A review of machine learning applications for the proton MR spectroscopy workflow.

This literature review presents a comprehensive overview of machine learning (ML) applications in proton MR spectroscopy (MRS). As the use of ML techniques in MRS continues to grow, this review aims to provide the MRS community with a structured overview of the state-of-the-art methods. Specifically, we examine and summarize studies published between 2017 and 2023 from major journals in the MR field. We categorize these studies based on a typical MRS workflow, including data acquisition, processing, analysis, and artificial data generation. Our review reveals that ML in MRS is still in its early stages, with a primary focus on processing and analysis techniques, and less attention given to data acquisition. We also found that many studies use similar model architectures, with little comparison to alternative architectures. Additionally, the generation of artificial data is a crucial topic, with no consistent method for its generation. Furthermore, many studies demonstrate that artificial data suffers from generalization issues when tested on in vivo data. We also conclude that risks related to ML models should be addressed, particularly for clinical applications. Therefore, output uncertainty measures and model biases are critical to investigate. Nonetheless, the rapid development of ML in MRS and the promising results from the reviewed studies justify further research in this field.

Time-encoded golden angle radial arterial spin labeling: Simultaneous acquisition of angiography and perfusion data.

The objective of the current study was to combine a time-encoded pseudocontinuous arterial spin labeling (te-pCASL) scheme with a golden angle radial readout for simultaneous acquisition of angiography and perfusion images from one single dataset, both in a highly flexible single-slice approach as well as within a multislice setting. A te-pCASL preparation and the golden angle radial readout were both used as a temporal resolution tool to retrospectively choose the temporal window for the reconstruction of both angiography and perfusion images from a single-slice dataset. The temporal window could be chosen retrospectively and adjusted to the hemodynamics of the volunteer on the scanner for the single-slice dataset. Angiographic images were reconstructed at a minimum temporal resolution of 69 ms. For the perfusion phase, only the densely sampled center of k-space was included in the reconstruction. For a multislice acquisition, the golden angle radial readout allowed reconstruction of images with different spatial resolutions to provide angiographic and perfusion information over 10 slices. The te-pCASL preparation was used as the only source for dynamic information. The multislice acquisition shows the ability of the golden angle radial readout to display the inflow of the labeled blood into the arteries as well as the perfusion in the tissue with full brain coverage. By combining a te-pCASL preparation with a golden angle radial readout, single-slice high temporal resolution angiography and good quality perfusion images were reconstructed in a flexible manner from a single dataset. Optimizing the golden angle radial readout for reconstructions at multiple spatial resolutions allows for multislice acquisition.

Distortion-matched T1 maps and unbiased T1-weighted images as anatomical reference for high-resolution fMRI.

The increasing availability of ultra-high field scanners has led to a growing number of submillimetre fMRI studies in humans, typically targeting the gray matter at different cortical depths. In most analyses, the definition of surfaces at different cortical depths is based on an anatomical image with different contrast and distortions than the functional images. Here, we introduce a novel sequence providing bias-field corrected T1-weighted images and T1-maps with distortions that match those of the fMRI data, with an image acquisition time significantly shorter than standard T1-weighted anatomical imaging. For 'T1-imaging with 2 3D-EPIs', or T123DEPI, 3D-EPI volumes are acquired centred at two inversion times. These 3D-EPIs are segmented into half, quarter or smaller blocks of k-space to allow for optimisation of the inversion times. T1-weighted images and T1-maps are then generated as for MP2RAGE acquisitions. A range of T123DEPI data acquired at 7 T is shown with resolutions ranging from 0.7 mm to 1.3 mm isotropic voxels. Co-registration quality to the mean EPI of matching fMRI timecourses shows markedly less local deviations compared to co-registration of a standard MP2RAGE to the same echo planar volume. Thus, the T123DEPI T1-weighted images and T1-maps can be used to provide cortical surfaces with matched distortions to the functional data or else to facilitate co-registration between functional and undistorted anatomical data.

A comparison of navigators, snap-shot field monitoring, and probe-based field model training for correcting B0 -induced artifacts in T2*-weighted images at 7 T.

PURPOSE: To compare methods for estimating B0 maps used in retrospective correction of high-resolution anatomical images at ultra-high field strength. The B0 maps were obtained using three methods: (1) 1D navigators and coil sensitivities, (2) field probe (FP) data and a low-order spherical harmonics model, and (3) FP data and a training-based model. METHODS: Data from nine subjects were acquired while they performed activities inducing B0 field fluctuations. Estimated B0 fields were compared with reference data, and the reductions of artifacts were compared in corrected T2* images. RESULTS: Reduction of sum-of-squares difference relative to a reference image was evaluated, and Method 1 yielded the largest artifact reduction: 27 ± 15%, 20 ± 18% (mean ± 1 standard deviation) for deep breathing and combined deep breathing and hand motion activities. Method 3 performed almost as well (24 ± 18%, 15 ± 17%), provided that adequate training data were used, and Method 2 gave a similar result (21 ± 16%, 19 ± 17%). CONCLUSION: This study confirms that all of the investigated methods can be used in retrospective image correction. In terms of image quality, Method 1 had a small advantage, whereas the FP-based methods measured the B0 field slightly more accurately. The specific strengths and weaknesses of FPs and navigators should therefore be considered when determining which B0 -estimation method to use. Magn Reson Med 78:1373-1382, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Brain histopathology in patients with systemic lupus erythematosus: identification of lesions associated with clinical neuropsychiatric lupus syndromes and the role of complement.

OBJECTIVES: Neuropsychiatric (NP) involvement is a poorly understood manifestation of SLE. We studied post-mortem histopathology in relation to clinical NPSLE syndromes and complement deposition in brains of NPSLE and SLE patients and controls. Furthermore, we investigated the correlation between cerebral post-mortem histopathology and ex vivo 7 T MRI findings in SLE and NPSLE. METHODS: A nationwide search for autopsy material yielded brain tissue from 16 NPSLE and 18 SLE patients. Brains obtained from 24 patients who died of acute cardiac events served as controls. Apart from a histopathological evaluation, paraffin-embedded cortical tissue was stained for components of the classical, lectin and terminal complement pathways. RESULTS: Diffuse vasculopathy, microinfarction, macroinfarction, vasculitis and microthrombi occurred significantly more often in NPSLE than SLE patients and were absent in controls. Focal vasculopathy was found in both SLE patients and controls. Complement deposition was strongly associated with both SLE and NPSLE, but not with controls (P < 0.001). Microthrombi were found uniquely in NPSLE and were associated with C4d and C5b-9 deposits (P < 0.05). A 7 T MRI was unable to detect most small vessel injury that was visible histopathologically. CONCLUSION: Our study demonstrates that histopathological lesions in NPSLE represent a continuum, ranging from non-specific lesions such as focal vasculopathy, to more specific lesions including C4d- and C5b-9-associated microthrombi and diffuse vasculopathy related to clinical syndromes defining NPSLE. Complement deposition may be a key factor in the interaction between circulating autoantibodies and thromboischaemic lesions observed in NPSLE. Therefore, complement inhibition may have novel therapeutic potential in NPSLE.

Diffusion-prepared stimulated-echo turbo spin echo (DPsti-TSE): An eddy current-insensitive sequence for three-dimensional high-resolution and undistorted diffusion-weighted imaging.

In this study, we present a new three-dimensional (3D), diffusion-prepared turbo spin echo sequence based on a stimulated-echo read-out (DPsti-TSE) enabling high-resolution and undistorted diffusion-weighted imaging (DWI). A dephasing gradient in the diffusion preparation module and rephasing gradients in the turbo spin echo module create stimulated echoes, which prevent signal loss caused by eddy currents. Near to perfect agreement of apparent diffusion coefficient (ADC) values between DPsti-TSE and diffusion-weighted echo planar imaging (DW-EPI) was demonstrated in both phantom transient signal experiments and phantom imaging experiments. High-resolution and undistorted DPsti-TSE was demonstrated in vivo in prostate and carotid vessel wall. 3D whole-prostate DWI was achieved with four b values in only 6 min. Undistorted ADC maps of the prostate peripheral zone were obtained at low and high imaging resolutions with no change in mean ADC values [(1.60 ± 0.10) × 10-3 versus (1.60 ± 0.02) × 10-3  mm2 /s]. High-resolution 3D DWI of the carotid vessel wall was achieved in 12 min, with consistent ADC values [(1.40 ± 0.23) × 10-3  mm2 /s] across different subjects, as well as slice locations through the imaging volume. This study shows that DPsti-TSE can serve as a robust 3D diffusion-weighted sequence and is an attractive alternative to the traditional two-dimensional DW-EPI approaches.

Passive radiofrequency shimming in the thighs at 3 Tesla using high permittivity materials and body coil receive uniformity correction.

PURPOSE: To explore the effects of high permittivity dielectric pads on the transmit and receive characteristics of a 3 Tesla body coil centered at the thighs, and their implications on image uniformity in receive array applications. THEORY AND METHODS: Transmit and receive profiles of the body coil with and without dielectric pads were simulated and measured in healthy volunteers. Parallel imaging was performed using sensitivity encoding (SENSE) with and without pads. An intensity correction filter was constructed from the measured receive profile of the body coil. RESULTS: Measured and simulated data show that the dielectric pads improve the transmit homogeneity of the body coil in the thighs, but decrease its receive homogeneity, which propagates into reconstruction algorithms in which the body coil is used as a reference. However, by correcting for the body coil reception profile this effect can be mitigated. CONCLUSION: Combining high permittivity dielectric pads with an appropriate body coil receive sensitivity filter improves the image uniformity substantially compared with the situation without pads. Magn Reson Med 76:1951-1956, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Measuring motion-induced B0 -fluctuations in the brain using field probes.

PURPOSE: Fluctuations of the background magnetic field (B0 ) due to body and breathing motion can lead to significant artifacts in brain imaging at ultrahigh field. Corrections based on real-time sensing using external field probes show great potential. This study evaluates different aspects of field interpolation from these probes into the brain which is implicit in such methods. Measurements and simulations were performed to quantify how well B0 -fluctuations in the brain due to body and breathing motion are reflected in external field probe measurements. METHODS: Field probe measurements were compared with scanner acquired B0 -maps from experiments with breathing and shoulder movements. A realistic simulation of B0 -fluctuations caused by breathing was performed, and used for testing different sets of field probe positions. RESULTS: The B0 -fluctuations were well reflected in the field probe measurements in the shoulder experiments, while the breathing experiments showed only moderate correspondence. The simulations showed the importance of the probe positions, and that performing full 3(rd) order corrections based on 16 field probes is not recommended. CONCLUSION: Methods for quantitative assessment of the field interpolation problem were developed and demonstrated. Field corrections based on external field measurements show great potential, although potential pitfalls were identified.

Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function.

Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aß)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2 *-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2 *-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aß plaques and associated iron. Cognitive tests and T2 *-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00-1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73-0.99; p < 0.001) and HC (mean, 0.94; range, 0.79-1.10; p < 0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (ß = -0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. Copyright © 2014 John Wiley & Sons, Ltd.

Diffusion-weighted chemical shift imaging of human brain metabolites at 7T.

PURPOSE: Diffusion-weighted chemical shift imaging (DW-CSI) of brain metabolites poses significant challenges associated with the acquisition of spectroscopic data in the presence of strong diffusion weighting gradients. We present a reproducible DW-CSI acquisition and processing scheme that addresses most of the potential sources of instability and provides reproducible and anatomically meaningful diffusion-weighted and apparent diffusion coefficient (ADC) metabolite maps. METHODS: A real-time navigator-based acquisition scheme was used, allowing instantaneous reacquisition of corrupted k-space data and postprocessing correction of gradient-induced phase fluctuations. Eddy current correction based on residual water resonance was implemented and improved the quality of the data significantly. RESULTS: Highly reproducible diffusion-weighted metabolite maps of three highest concentration brain metabolites are shown. The navigator-based accept/reject strategy and the postacquisition corrections improved the stability of the DW-CSI signal and the reproducibility of the resulting DW-CSI maps significantly. The metabolite ADC values could be related to the underlying tissue cellular composition. CONCLUSION: Robust investigation of DW-CSI of brain metabolites is feasible and may provide information complementary to that obtained from more sensitive but less specific methods such as diffusion tensor imaging.

An automated tool for cortical feature analysis: Application to differences on 7 Tesla T2* -weighted images between young and older healthy subjects.

PURPOSE: High field T2* -weighted MR images of the cerebral cortex are increasingly used to study tissue susceptibility changes related to aging or pathologies. This paper presents a novel automated method for the computation of quantitative cortical measures and group-wise comparison using 7 Tesla T2* -weighted magnitude and phase images. METHODS: The cerebral cortex was segmented using a combination of T2* -weighted magnitude and phase information and subsequently was parcellated based on an anatomical atlas. Local gray matter (GM)/white matter (WM) contrast and cortical profiles, which depict the magnitude or phase variation across the cortex, were computed from the magnitude and phase images in each parcellated region and further used for group-wise comparison. Differences in local GM/WM contrast were assessed using linear regression analysis. Regional cortical profiles were compared both globally and locally using permutation testing. The method was applied to compare a group of 10 young volunteers with a group of 15 older subjects. RESULTS: Using local GM/WM contrast, significant differences were revealed in at least 13 of 17 studied regions. Highly significant differences between cortical profiles were shown in all regions. CONCLUSION: The proposed method can be a useful tool for studying cortical changes in normal aging and potentially in neurodegenerative diseases. Magn Reson Med 74:240-248, 2015. © 2014 Wiley Periodicals, Inc.

Time-efficient interleaved human (23)Na and (1)H data acquisition at 7 T.

The aim of this study was to implement and evaluate a flexible and time-efficient interleaved imaging approach for the acquisition of proton and sodium images of the human knee at 7 T within a clinically relevant timescale. A flexible software framework was established which allowed the interleaving of multiple, different, fully specific absorption ratio (SAR)-validated scans. The system was able to switch between these different scans at flexible time points. The practical example presented consists of interleaved proton (Dixon imaging and T2* mapping) and sodium (mapping the sodium content and fluid-suppressed component separately) sequences with the key idea to perform proton MRI whilst the sodium nuclei relax towards thermal equilibrium, and vice versa. Comparisons were made between these four scans being acquired sequentially in the normal mode of scanner operation and those acquired in an interleaved fashion. Images acquired in the interleaved mode were very similar to those acquired in sequential scans with no image artifacts produced by the slight intra-sequence variation in steady-state magnetization. A reduction in scanning time of almost a factor of two was established using the interleaved scans, allowing such a protocol to be completed within 30 min. Phantom experiments and in vivo scans performed in healthy volunteers and in one patient proved the basic feasibility of this approach. This approach for the interleaving of multiple proton and sodium scans, each with different contrasts, is an efficient method for the design of new practical clinical protocols for sodium MRI.

Fast multistation water/fat imaging at 3T using DREAM-based RF shimming.

PURPOSE: To show the effect, efficiency, and image quality improvements achievable by Dual Refocusing Echo Acquisition Mode (DREAM)-based B1+ shimming in whole-body magnetic resonance imaging (MRI) at 3T using the example of water/fat imaging. MATERIALS AND METHODS: 3D multistation, dual-echo mDixon gradient echo imaging was performed in 10 healthy subjects on a clinical 3T dual-transmit MRI system using station-to-station adapted B1+ shimming based on fast DREAM B1+ mapping. Whole-body data were obtained using conventional quadrature excitation and station-by-station adapted DREAM-based B1+ shimmed excitation, along with the corresponding B1+ maps for both excitation modes to assess image quality and radiofrequency (RF) performance. RESULTS: Station-dependent DREAM-based B1+ shimming showed significantly improved image quality in the stations covering the upper legs, pelvis, and upper body region for all subjects (P < 0.02). This finding is supported by corresponding B1+ maps showing an improved B1+ homogeneity and a more precise flip angle in the DREAM-based B1+ shimmed excitation (P < 0.01). Furthermore, the very short dual-channel DREAM B1+ mapping times of less than 2 seconds facilitate quick B1+ shimming. CONCLUSION: Station-dependent DREAM-based B1+ shimming improved RF performance and image quality and is therefore a promising technique for whole-body multistation imaging applications.

Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging.

PURPOSE: To assess the prevalence and number of cortical microinfarcts in patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR) imaging system, to assess the independent association of cortical microinfarcts with cognitive dysfunction, and to investigate potential confounding effects of the coexisting presence of cerebral amyloid angiopathy (CAA). MATERIALS AND METHODS: The local institutional review board approved this study. In all cases, informed consent was obtained. High-spatial-resolution fluid-attenuated inversion recovery and T2*-weighted images were acquired in 14 AD patients and 18 control subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA was assessed according to the Boston criteria. Image analysis was performed independently by two reviewers. Mann-Whitney U test was performed to assess differences in number of microinfarcts between groups. Negative binomial regression models were used to assess the association between diagnosis of AD and diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number of microbleeds and number of microinfarcts, and between cognitive function and number of microinfarcts, all corrected for age and sex. RESULTS: Interobserver agreement was excellent for detecting microinfarcts (κ = 0.91) (P < .001). Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean, 7.2) compared with control subjects (mean, 1.8). Negative binomial regression models showed an independent association between AD and number of microinfarcts (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative correlation was found between cognitive function and the number of microinfarcts (P = .009). CONCLUSION: Patients with AD show more microinfarcts than do control subjects, the number of microinfarcts correlates with global cognitive performance, and the presence of microinfarcts was mainly AD rather than CAA related.

Volumetric B1 (+) mapping of the brain at 7T using DREAM.

PURPOSE: To tailor and optimize the Dual Refocusing Echo Acquisition Mode (DREAM) approach for volumetric B1 (+) mapping of the brain at 7T. THEORY AND METHODS: A new DREAM echo timing scheme based on the virtual stimulated echo was derived to minimize potential effects of transverse relaxation. Furthermore, the DREAM B1 (+) mapping performance was investigated in simulations and experimentally in phantoms and volunteers for volumetric applications, studying and optimizing the accuracy of the sequence with respect to saturation effects, slice profile imperfections, and T1 and T2 relaxation. Volumetric brain protocols were compiled for different isotropic resolutions (5-2.5 mm) and SENSE factors, and were studied in vivo for different RF drive modes (circular/linear polarization) and the application of dielectric pads. RESULTS: Volumetric B1 (+) maps with good SNR at 2.5 mm isotropic resolution were acquired in about 20 s or less. The specific absorption rate was well below the safety limits for all scans. Mild flow artefacts were observed in the large vessels. Moreover, a slight contrast in the ventricle was observed in the B1 (+) maps, which could be attributed to T1 and T2 relaxation effects. CONCLUSION: DREAM enables safe, very fast, and robust volumetric B1 (+) mapping of the brain at ultrahigh fields.

Cortical phase changes in Alzheimer's disease at 7T MRI: a novel imaging marker.

BACKGROUND: Postmortem studies have indicated the potential of high-field magnetic resonance imaging (MRI) to visualize amyloid depositions in the cerebral cortex. The aim of this study is to test this hypothesis in patients with Alzheimer's disease (AD). METHODS: T2*-weighted MRI was performed in 16 AD patients and 15 control subjects. All magnetic resonance images were scored qualitatively by visual assessment, and quantitatively by measuring phase shifts in the cortical gray matter and hippocampus. Statistical analysis was performed to assess differences between groups. RESULTS: Patients with AD demonstrated an increased phase shift in the cortex in the temporoparietal, frontal, and parietal regions (P < .005), and this was associated with individual Mini-Mental State Examination scores (r = -0.54, P < .05). CONCLUSION: Increased cortical phase shift in AD patients demonstrated on 7-tesla T2*-weighted MRI is a potential new biomarker for AD, which may reflect amyloid pathology in the early stages.

Subject tolerance of 7 T MRI examinations.

PURPOSE: To determine the subjective experiences and the sources of discomfort for subjects undergoing 7 T magnetic resonance imaging (MRI) examinations on a whole-body 7 T system in a hospital setting MATERIALS AND METHODS: A postscan survey was filled out by 101 healthy subjects who participated in a 7 T examination. All participants answered questions regarding different potential sensations of discomfort including dizziness, claustrophobia, and scanner noise. RESULTS: Dizziness was reported most frequently, with 34% of subjects experiencing dizziness while moving into the scanner and 30% while moving out of the magnet. Scanner noise was also frequently mentioned as uncomfortable (33% of the subjects). In 11% of the cases a metallic taste was reported. The overall experience was rated by 3% as unpleasant, 51% as neutral, and 46% as pleasant. CONCLUSION: The reported side effects are larger than previously reported for lower field strengths. However, overall, 7 T examinations are well tolerated, with only 3% of subjects rating it as unpleasant. These results agree well with previous in-depth studies, and provide further evidence that 7 T MRI would be accepted by patients in clinical practice.

Elevated brain iron is independent from atrophy in Huntington's Disease.

Increased iron in subcortical structures in patients with Huntington's Disease (HD) has been suggested as a causal factor of neuronal degeneration. The present study examines iron accumulation, measured using magnetic resonance imaging (MRI), in premanifest gene carriers and in early HD patients as compared to healthy controls. In total 27 early HD patients, 22 premanifest gene carriers and 25 healthy controls, from the Leiden site of the TRACK-HD study, underwent 3T MRI including high resolution 3D T(1)- and T(2)-weighted and asymmetric spin echo (ASE) sequences. Magnetic Field Correlation (MFC) maps of iron levels were constructed to assess magnetic field inhomogeneities and compared between groups in the caudate nucleus, putamen, globus pallidus, hippocampus, amygdala, accumbens nucleus, and thalamus. Subsequently the relationship of MFC value to volumetric data and disease state was examined. Higher MFC values were found in the caudate nucleus (p<0.05) and putamen (p<0.005) of early HD compared to controls and premanifest gene carriers. No differences in MFC were found between premanifest gene carriers and controls. MFC in the caudate nucleus and putamen is a predictor of disease state in HD. No correlation was found between the MFC value and volume of these subcortical structures. We conclude that Huntington's disease patients in the early stages of the disease, but not premanifest gene carriers, have higher iron concentrations in the caudate nucleus and putamen. We have demonstrated that the iron content of these structures relates to disease state in gene carriers, independently of the measured volume of these structures.

Differences in apparent diffusion coefficients of brain metabolites between grey and white matter in the human brain measured at 7 T.

Diffusion weighted spectroscopy can provide microstructural information that is specific to compartmental geometry. So far, in human brain, apparent diffusion coefficients (ADCs) of only the metabolites N-acetyl aspartate, creatine (tCr) and choline (tCho) have been assessed. High field MR at 7 T allows the collection and analysis of diffusion weighted spectroscopy data of additional metabolites of interest such as glutamate (Glu), N-acetyl aspartyl glutamate, and glutamine (Gln), which are of interest due to their different compartmentalization and role in brain physiology. In this study, we performed (1)H diffusion weighted spectroscopy at 7 T using a diffusion-weighted PRESS sequence in parietal white matter (n = 6) and occipital grey matter (n = 7). Data were analyzed using the LCmodel. ADCs could reliably be obtained of N-acetyl aspartate, tCr, tCho, Glu, Gln in grey and white matter, and N-acetyl aspartyl glutamate in white matter. Significant differences in ADC values were observed between grey and white matter for all metabolites. ADCs in grey matter were consistently lower than in white matter. These differences can probably be attributed to different compartmentalization as well as to the differential impact of diffusion time on ADC of different molecules under conditions of restricted diffusion.

7 T MRI reveals diffuse iron deposition in putamen and caudate nucleus in CADASIL.

OBJECTIVE: Diffuse iron deposition in the brain is commonly found in older people. One of the possible mechanisms that contribute to this iron deposition is cerebral small vessel disease. The aim of this study is to quantify diffuse iron deposition in patients with the hereditary small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). METHODS: 25 NOTCH3 mutation carriers and 18 healthy controls were examined using high-resolution T2*-weighted imaging on a 7 T whole body MRI scanner. Susceptibility-weighted MRI scans were analysed for areas of signal loss and increased phase shift. Phase shift measurements in deep grey nuclei, cortex and subcortical white matter were compared between mutation carriers and controls. For confirmation, ex vivo brain specimens from another three patients with CADASIL were analysed for iron deposition using ex vivo MRI combined with iron histochemistry. RESULTS: In vivo MRI showed areas of decreased signal intensity and increased phase shift in mutation carriers. Compared with healthy controls, mutation carriers had significantly higher phase shift in the putamen (p=0.0002) and caudate nucleus (p=0.006). Ex vivo MRI showed decreased signal intensity in the putamen and caudate nucleus in all specimens. Histochemistry confirmed the presence of iron deposition in these nuclei. CONCLUSIONS: This study demonstrates increased diffuse iron accumulation in the putamen and caudate nucleus in patients with the small vessel disease CADASIL. This supports the hypothesis that small vessel disease contributes to the process of increased iron accumulation in the general population.